Malaria is a significant threat throughout the developing world. Among the most fascinating aspects of the protozoan parasites responsible for this disease are the methods they employ to avoid the immune system and perpetuate chronic infections. Key among these is antigenic variation: By systematically altering antigens that are displayed to the host's immune system, the parasite renders the adaptive immune response ineffective. For Plasmodium falciparum, the species responsible for the most severe form of human malaria, this process involves a complicated molecular mechanism that results in continuously changing patterns of variant-antigen-encoding gene expression. Although many features of this process remain obscure, significant progress has been made in recent years to decipher various molecular aspects of the regulatory cascade that causes chronic infection.